Most previous studies on this topic used a retrospective case-control design or indirect measures of exposure (pharmacy records). In this prospective study, 31,602 women were asked at their first prenatal visit about the use of Bendectin; 2,711 women reported use in the first trimester. The odds ratio (and 95% interval estimates) for major malformations was 1.05 (0.78-1.40). When individual malformations were evaluated, Bendectin use was statistically associated with microcephaly (5.33 (1.61-17.7)), cataract (5.33 (0.98-29.1)), and lung malformations (4.58 (1.76-11.9)). Since it is not clear whether these associations are due to the use of Bendectin or to the indication (vomiting) for which the drug was prescribed, the association between vomiting and these malformations was studied using previously published data from the Collaborative Perinatal Project. In that study, vomiting was associated with microcephaly (3.3 (1.1, 9.8)) and cataract (3.5 (0.8-16.1)). Vomiting was associated with these two malformations only among nonusers of Bendectin. Lung malformations were not associated with vomiting during pregnancy (1.3 (0.8-2.1)). These data strongly suggest that Bendectin is not associated with these malformations, however the possibility that vomiting is associated with microcephaly and cataract is suggested.